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INTRODUCTION AND OBJECTIVE:The management of traumatic renal injury has evolved over time, with increasing recognition that a majority of renal injuries can be safely managed conservatively. Althou...

To review the current literature on acute management of traumatic penile fracture, with a specific discussion of those injuries following collagenase clostridium histolyticum (CCH) injections for the treatment of Peyronie’s disease. The immediate repair of traumatic penile fracture injury is associated with significantly better prognosis for long-term sexual health. Corporal disruption following CCH administration has several distinct features, and the trend is to manage these patients conservatively in the absence of urethral injury. Traumatic penile fracture repair continues to have excellent results when performed immediately following injury. The post-CCH treatment setting portends increased difficulty during surgical management and can be successfully managed in most cases by conservative measures.

To review the current literature on acute management of traumatic penile fracture, with a specific discussion of those injuries following collagenase clostridium histolyticum (CCH) injections for the treatment of Peyronie's disease.The immediate repair of traumatic penile fracture injury is associated with significantly better prognosis for long-term sexual health. Corporal disruption following CCH administration has several distinct features, and the trend is to manage these patients conservatively in the absence of urethral injury. Traumatic penile fracture repair continues to have excellent results when performed immediately following injury. The post-CCH treatment setting portends increased difficulty during surgical management and can be successfully managed in most cases by conservative measures.

The treatment for penile cancer has been shown to cause harmful psychiatric symptoms as well as have detrimental effects on well-being. In the past several years, alternatives to total or partial penectomy have emerged, such as chemotherapy, radiation, penile sparing, and laser ablation therapies. A more specific breakdown for penile cancer is in order as the therapy has the potential for life changing surgery. We examined the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013), comprising 28% of the United States population. International Classification of Diseases, Tenth revision codes C60.8-C60.9 and the International Classification of Diseases-Oncology codes 8010/2, 8010/3, 8051/2, 8051/3, 8052/2, 8052/3, 8070/2, 8070/3-8072/3, 8074/3, 8076/3, and 8083/3-8084/3 were used. Age, race, marital status, and clinicopathologic variables were studied. We used contingency tables of suicide rates; mid-P exact test was used for analysis. There were 13 suicides noted in 6155 patients with squamous cell carcinoma of the penis. All patients that committed suicide had undergone a surgical intervention. Certainly, penile cancer after treatment has a powerful effect on quality of life as increased depression and sexual anxiety have been documented in postoperative patients. This is in contrast to the observed suicide rate. Despite the reported negative psychological effects in patients with penile cancer, suicide rates are among the lowest of all urologic malignancies.

210 Background: The UroNav fusion biopsy system allows for the real time visualization of the prostate using multi-parametric MRI (mpMRI) data. This technology has become a valuable instrument for staging prostate cancer at the time of PSA elevation. However, data is still yet emerging over the use of this tool for patients currently being followed on an active surveillance (AS) protocol. In this study we sought to evaluate the efficacy of the UroNav system in patients on AS. Methods: Patients were enrolled into our prospective study, at a single center institution, approved by the Southeast Louisiana Veterans Health Care System (SLVHCS) IRB. Inclusion criteria for this study was men previously enrolled in an active surveillance protocol with a life expectancy ≥10 years. Statical analysis was performed using R 4.0.2 (Ann Arbor, MI). Results: A total of 103 patients were entered into this study for analysis. These patients had a median age of 67.1(62.8 - 70.8) and BMI of 28.6(25.5 - 32.3). The clinical profiles of these patients were median PSA of 6.36(4.65 - 8.89) with a velocity slope of (0.065 (-0.14 - 0.27), TRUS volume of 39.5(32.2 - 56.8), PSAD of 0.15(0.09 - 0.23), and a PI-RAD score of 4(3 – 5). A logistic regression was performed using upgrading on UroNav or Template bx as the outcome. Patients with an increased PSA were more likely to upgrade of Bx (OR = 1.2 (1.05 - 1.39)). Additionally, patients with decreasing MRI volumes were also more likely to upgrade on Bx (OR = 0.97 (0.94 - 0.98)). A total of 42 (40%) patients upgraded on either MRI or Template bx from their initial AS workup. MRI found 13 (12.6%) patients with an upgraded GG that displayed consistent or benign disease on template. Conversely, template also found 13 (12.6%) unique patients who upgraded but were found to have constant or benign disease on mpMRI. Conclusions: mpMRI guided biopsy is a useful tool that can further assist physicians in characterizing prostate cancer in patients being concurrently followed on an active surveillance protocol. MRI is able to find clinically significant cancer that would have otherwise been missed on traditional template biopsies. [Table: see text]

Critically short telomeres activate p53-mediated apoptosis, resulting in organ failure and leading to malignant transformation. Mutations in genes responsible for telomere maintenance are linked to a number of human diseases. We derived induced pluripotent stem cells (iPSCs) from 4 patients with aplastic anemia or hypocellular bone marrow carrying heterozygous mutations in the telomerase reverse transcriptase (TERT) or the telomerase RNA component (TERC) telomerase genes. Both mutant and control iPSCs upregulated TERT and TERC expression compared with parental fibroblasts, but mutant iPSCs elongated telomeres at a lower rate compared with healthy iPSCs, and the deficit correlated with the mutations' impact on telomerase activity. There was no evidence for alternative lengthening of telomere (ALT) pathway activation. Elongation varied among iPSC clones derived from the same patient and among clones from siblings harboring identical mutations. Clonal heterogeneity was linked to genetic and environmental factors, but was not influenced by residual expression of reprogramming transgenes. Hypoxia increased telomere extension in both mutant and normal iPSCs. Additionally, telomerase-mutant iPSCs showed defective hematopoietic differentiation in vitro, mirroring the clinical phenotype observed in patients and demonstrating that human telomere diseases can be modeled utilizing iPSCs. Our data support the necessity of studying multiple clones when using iPSCs to model disease.

Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nω-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress. Antioxid. Redox Signal. 11, 25–33.

Background/Aims: Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart. Methods: Heart failure was created by an arteriovenous fistula (AVF). Mice were divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was supplemented with drinking water for 6 weeks in the appropriate surgery groups after surgery. Results: M-mode echocardiograms showed ventricular contractile dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9, and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase VI expression; however, STS supplementation reversed these effects in AVF mice. Among 2 enzymes that produce endogenous hydrogen sulfide (H2S), cystathionine-γ-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-β-synthase (CBS) expression. In addition, reduced production of H2S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H2S when AVF mice were supplemented with STS compared to AVF alone. Conclusions: These results suggested that STS modulated cardiac dysfunction and the extracellular matrix, in part, by increasing ventricular H2S generation.

By pumping a small cryogenic cell with a 40-nsec, 1-MeV e-beam pulse, we have excited lasing in dilute mixtures of xenon or krypton in liquid argon. The lasing occurred at 175 nm for the excimer Xe(2) and at 147 nm for Kr(2).

Thomas P Vacek, Utpal Sen, Neetu Tyagi, Jonathan C Vacek, Munish Kumar, et alDepartment of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky – 40202, USAAbstract: High plasma homocysteine levels are a known risk factor in heart failure and sudden cardiac death. The G proteins, Gs (stimulatory) and Gi (inhibitory), are involved in calcium regulation; overexpression has pathological consequences. The aims of this study were to examine the differential expression of Gs G protein and Gi in the hearts of hyperhomocysteinemic (Hhcy) mice, and to determine if homocysteine (Hcy) acts as an agonist in cell culture to mediate the change in G protein isoforms. To create Hhcy, heterozygous cystathionine-β-synthase (CBS) knockout (KO) mice were used. Mice were sacrificed, hearts were excised, cardiac tissue homogenates were prepared, and Western blots were performed. The results suggested that Gs G protein was downregulated in cardiac tissue of heterozygous CBS KO mice to 46% that of control hearts. However, the intracellular Gi G protein content remained the same in heterozygous CBS KO mice. Transformed cardiomyocyte HL-1 cells were treated with varying concentrations of homocysteine. The results suggested no detectable differential Gs and Gi expression. This suggested that Hcy did not act as an agonist in vitro to alter G protein content, but that Hcy produced some other in vivo effects to incur these results.Keywords: homocysteine, G proteins, heart failure, GPCR, HL-1

Hyperhomocysteinemia (HHcy) is associated with atherosclerotic events involving the modulation of arachidonic acid (AA) metabolism and the activation of matrix metalloproteinase-9 (MMP-9). Cytochrome P450 (CYP) epoxygenase-2J2 (CYP2J2) is abundant in the heart endothelium, and its AA metabolites epoxyeicosatrienoic acids (EETs) mitigates inflammation through NF-kappabeta. However, the underlying molecular mechanisms for MMP-9 regulation by CYP2J2 in HHcy remain obscure. We sought to determine the molecular mechanisms by which P450 epoxygenase gene transfection or EETs supplementation attenuate homocysteine (Hcy)-induced MMP-9 activation. CYP2J2 was over-expressed in mouse aortic endothelial cells (MAECs) by transfection with the pcDNA3.1/CYP2J2 vector. The effects of P450 epoxygenase transfection or exogenous supplementation of EETs on NF-kappabeta-mediated MMP-9 regulation were evaluated using Western blot, in-gel gelatin zymography, electromobility shift assay, immunocytochemistry. The result suggested that Hcy downregulated CYP2J2 protein expression and dephosphorylated PI3K-dependent AKT signal. Hcy induced the nuclear translocation of NF-kappabeta via downregulation of IKbetaalpha (endogenous cytoplasmic inhibitor of NF-kappabeta). Hcy induced MMP-9 activation by increasing NF-kappabeta-DNA binding. Moreover, P450 epoxygenase transfection or exogenous addition of 8,9-EET phosphorylated the AKT and attenuated Hcy-induced MMP-9 activation. This occurred, in part, by the inhibition of NF-kappabeta nuclear translocation, NF-kappabeta-DNA binding and activation of IKbetaalpha. The study unequivocally suggested the pivotal role of EETs in the modulation of Hcy/MMP-9 signal.

Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart.Heart failure was created by an arteriovenous fistula (AVF). Mice were divided into 4 groups: sham, AVF, sham + STS, and AVF + STS. STS (3 mg/ml) was supplemented with drinking water for 6 weeks in the appropriate surgery groups after surgery.M-mode echocardiograms showed ventricular contractile dysfunction with reduced aortic blood flow in AVF mice, whereas STS treatment prevented the decline in cardiac function. Ventricular collagen, MMP-2 and -9, and TIMP-1 were robustly increased with a decreasing trend in adenylate cyclase VI expression; however, STS supplementation reversed these effects in AVF mice. Among 2 enzymes that produce endogenous hydrogen sulfide (H(2)S), cystathionine-gamma-lyase (CSE) expression was attenuated in AVF mice with no changes in cystathionine-beta-synthase (CBS) expression. In addition, reduced production of H(2)S in AVF ventricular tissue was normalized with STS supplementation. Moreover, cardiac tissues were more responsive to H(2)S when AVF mice were supplemented with STS compared to AVF alone.These results suggested that STS modulated cardiac dysfunction and the extracellular matrix, in part, by increasing ventricular H(2)S generation.

The number of IVHS Commercial Vehicle Operations (CVO) systems may be much larger than what might be expected. When compared to the coverage given to consumer IVHS demonstrations, the lack of awareness of commercial systems is understandable. In fact, there are hundreds of installations of commercial systems world-wide. While the goals of each application vary with the user, these systems are generally used for Computer-Aided-Dispatching (CAD) and remote access to host computer databases. The system users include police and fire departments, trucking companies, taxi companies, intermodal ports, and utilities. These organizations are experiencing the benefits of increased safety, better efficiency, and improved service. CVO systems fundamentally change the way the mobile work force relates to the organization and, in turn, affect the way the organization functions. A brief history of CVO installations, a review of design issues, and user justification are presented. In addition, those implementing consumer IVHS systems can learn valuable lessons from previous installations. Although there are distinct differences between commercial and consumer IVHS, much can be learned about technology and user acceptance.

Population inversion is observed between the field-independent ground hyperfine states of Rb-87 when using an optical pumping technique which is applicable to a large number of species of atoms and ions. Inversion occurs upon a coherent transfer of angular momentum to the Rb-87 spin system from circularly polarized light propagating in a transverse direction to a magnetic field. Coherence is established by modulating, at certain frequencies, the light intensity or magnetic-field strength.

Electron beam excitation of high‐pressure argon has resulted in the first demonstration of laser action from molecular argon at 126.1±0.3 nm. Strong laser action was achieved at pressures up to 6.89 MPa (1000 psia).

Vacuum ultraviolet (VUV) photolysis of N2O immersed in high‐pressure Ar has been used to produce O(1S0) at high density. A two‐chamber apparatus was used to prevent the effects of electron and ion collision in the experimental volume, thereby providing a much clearer kinetic situation. The gain profile and stimulated emission cross section near 558 nm and the upper‐state lifetime were determined for ArO.

Electron beam excitation of pure Xe and Xe–Ar and Xe–Ne gas mixtures have been studied. Significant differences in the temporal character of ultraviolet output were observed. Under the best conditions laser output of 75‐MW peak power and 0.76‐J output energy were achieved. The molecular xenon laser is established as having the highest power in the wavelength region short of red.

Experiments have been conducted on high‐pressure Xe gas undergoing excitation by a high‐current pulsed relativistic electron beam. Spectral, temporal, and calorimetric diagnostics were performed. The results establish that lasing in molecular Xe has been achieved with the highest laser power yet obtained in the vacuum ultraviolet. Premature termination of light output indicates the possibility of significant effects due to thermal collisions.

The purpose of this study was to evaluate the role of gastrin in the genesis of lower esophageal sphincter (LES) pressure by the use of a high titer gastrin antiserum. Intravenous infusions of increasing amounts of rabbit gastrin antiserum, but not control antiserum, produced graded reductions in the resting LES pressure in anesthetized opossums. A maximal inhibition in LES pressure of 80.0±3.1% (mean ±SE) was achieved when gastrin antiserum was administered in an amount estimated to bind almost all endogenous circulating gastrin in the opossum. Gastrin antiserum also inhibited the LES response to endogenous gastrin release (gastric deacidification) and to exogenous intravenous administration of gastrin I. The inhibition of the LES response to exogenous gastrin I by gastrin antiserum could be eliminated by giving excess gastrin I. Studies performed in vitro showed that gastrin antiserum inhibited the contractile response of LES circular muscle to gastrin I, but not to acetylcholine. These studies indicate that gastrin antiserum: (a) specifically antagonized the response of LES circular muscle to gastrin, in vitro; (b) diminished the LES response to the endogenous release and to the exogenous administration of gastrin; and (c) markedly reduced the resting level of LES pressure. We conclude that endogenous gastrin is the major determinant of resting LES pressure.

Intraluminal manometric studies were carried out in 19 patients with untreated achalasia and in 20 normals. Lower esophageal sphincter (LES) pressure was 50.5 ±4.6 mm Hg in patients with achalasia as compared with 19.4 ±1.3 mm Hg in the normal group. In both groups, the LES pressure was lowered when exogenous 0.1 N HCl was placed into the stomach. Although the nadir of pressure attained with acid suppression was the same, the per cent inhibition was significantly greater in patients with achalasia. Serum gastrin levels were the same in the two groups studied. The patients with achalasia, pre- and postpneumatic dilatation, showed a supersensitivity to exogenous intravenous gastrin I, as compared with normals. These data suggest that high, acid-suppressible levels of LES pressure, in patients with achalasia, are due to supersensitivity to endogenous gastrin.

Vacuum ultraviolet emission from high-pressure Xe gas under excitation by a pulsed electron beam has been investigated. When cavity mirrors were provided, significant line narrowing and a thousandfold increase in spectral intensity occurred at 1730 ± 10 A. This was accompanied by severe mirror burning and provides strong evidence that an associative molecular Xe laser has been achieved.

We have lased XeO at 547 nm with xenon and N(2)O concentrations of tens of parts in 10(6) in liquid argon. The solution was pumped with a short-pulse 1-MeV e beam. The resulting gain was at least 23% per centimeter.